The purpose of this investigation is to elucidate the connectional and cellular mechanisms underlying those aspects of motor and learning processes which are organized by cingulate cortex. The increase in neuronal spike activity in cungulate cortex during acquisition of active avoidance behaviors is dependent on connections between the anterior thalamic nuclei and posterior cingulate cortex. These and other response sequences will be interpreted according to connections amoung specific classes of neurons, the action of the putative thalamocortical neurotransmitter acetylcholine (ACh) and histological localization of ACh receptors. The following experiments will be performed. First, using a Golgi-electron microscopic procedure in rats with anterior thalamic lesions, the postsynaptic neurons to this afferent will be defined. Second, association of ACh receptors with thalamocortical terminals will be assessed by plcing thalamic lesions in rtats and then determining specific Alpha-bungarotoxin and propylbenzylcholine mustard binding two weeks later in vitro using light microscopic autoradiography. Third, neurons that are GABAergic will be identified with a combined 3H-GABA uptake and Golgi, gold-toning procedure. Fourth, the action of ACh on cingulate neurons will be analyzed in a cortical slice preparation using intracellular recording and marking techniques. Observed changes in input resistance, resting membrane potential and spike generation as well as interactions of ACh-evoked response(s) with excitatory and inhibitory intracortical connections will be evaluated and related to morphologically identified neurons. The data from these experiments will provide a basis for the first comprehensive circuit diagram of mammalian cingulate cortex, including localization of ACh receptors and determination of ACh-evoked responses. Since cholinomimetic drugs are presently being employed clinically with varying degrees of sccess to alleviate certain motor and memory disorders, an understanding of the cingulate cortex link in the limbic cholinergic system may eventually provide a basis for refining this therapy.